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Objective: To systematically evaluate the efficacy and safety of Xuebijing injection in the treatment of vascular endothelial injury in sepsis, and to provide evidence-based reference for clinical medication. Methods: The randomized controlled trials of Xuebijing injection combined with conventional treatment (experimental group) versus conventional treatment (control group) for sepsis were collected by computer search of Chinese CNKI database, WANFANG database, and VIP database. Literature screening was performed according to the inclusion and exclusion criteria. According to the Cochrane International Collaboration Evaluator Workbook procedure, the quality evaluation and bias analysis were performed for the literatures included in the meta-analysis. Revman 5.3 software was used for systematic metaanalysis. Results: A total of 15 clinical randomized controlled trials with a total of 930 patients were included. Meta-analysis showed that Xuebijing injection combined with conventional therapy could reduce 28-day mortality in sepsis[OR=0.52,95％CI(0.38,0.71),P<0.0001], APACHE Ⅱ integral [WMD=-2.65,95％CI(-3.23, -2.08),P<0.00001]; be effective in decreasing D-dimer [WMD=-0.79,95％CI(-1.17,-0.40),P<0.0001], TNF-α[WMD=-36.71,95％ CI(-43.04,-30.39),P<0.00001], vWF[WMD=-15.94,95％CI(-27.60,-4.28),P=0.007],sEselectin[ WMD=-118.30,95％CI(-139.65,-96.95),P<0.00001], ESM-1[WMD=-135.44,95％ CI(-186.30,-84.57),P<0.00001], sTM[WMD=-56.46,95％CI(-66.39,-46.53),P<0.00001]; can effectively increase platelets [WMD=30.78,95％CI(25.65, 35.92),P<0.00001]. Conclusion: Xuebijing injection can not only effectively reduce the release of inflammatory factors, thereby improving vascular endothelial injury, reducing coagulation disorders and blocking coagulation-inflammation network; it can also increase the level of platelets, thereby repairing injured vascular endothelial cells, which has a certain value to reduce the condition of sepsis and improve the prognosis. It also provides some basis for the treatment of sepsis secondary to novel coronavirus pneumonia. [ABSTRACT FROM AUTHOR]

The global incidence of sepsis is increasing, and mortality remains high. The mortality is even higher in resource-poor countries where facilities and equipment are limited. The Surviving Sepsis Campaign (SSC) recommends an updated hour-1 bundle based on the evidence from the International Guidelines for Management of Sepsis and Septic Shock 2018. To reduce mortality from sepsis, compliance with the "bundle" is essential. Data from developing countries like Sri Lanka on the management of sepsis according to the SSC guidelines are not available. Hence, this study looks at the patient characteristics and management of septic patients at a tertiary care hospital in Sri Lanka. Patients admitted to the University Medical Unit of Colombo South Teaching Hospital from January to August 2019 fulfilling the inclusion criteria were included. The hour-1 sepsis bundle adherence, demographic data, and management were recorded. There were 387 patients: 163 males and 224 females. The age range was 15-95 with a mean age of 63. 83.7% were direct admissions while 16.3% were transfers from a peripheral hospital. The most common source of infection was urine (82 (21.2%)) followed by blood stream (105 (27.1%)) and skin and soft tissue (114 (29.5%)). One-hour SSC bundle compliance is as follows: administration of intravenous fluids: 42 (10.9%), blood cultures before antibiotics: 225 (58.1%), first dose antibiotic: 15 (3.9%), and arterial blood gas: 60 (15.5%). Staffing capacity did not make a difference to adherence to the bundle. The study mortality rate was 37 (9.6%). Binary logistic regression indicates that quick sequential organ failure assessment (qSOFA) score is a significant predictor of mortality (chi ‐ square = 35.08 , df = 3 , and p = 0.001 (<0.05)) with an odds ratio (OR) of 7.529 (95% CI 3.597-14.323). The other predictors, age, sex, adherence to sepsis care bundle, and comorbidities, were not significant. In conclusion, mortality of sepsis is high and adherence to sepsis care bundle is poor in Sri Lanka even at a tertiary care hospital. Education and training of staff are needed to boost adherence. This will in turn improve quality of care and outcomes of septic patients in resource-poor countries. [ABSTRACT FROM AUTHOR]

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This present research work reports the possible effects and the underlying mechanism of atorvastatin on survival rate and cognitive disorders after sepsis. Sepsis is a life-threatening dysfunction that arises when the body's response to infection causes injury to its own tissues and organs. Diffuse sepsis was induced by cecal ligation and puncture surgery (CLP) in ICR mice. 0.2 mg/kg body weight of atorvastatin was administrated intraperitoneally at 12 h before surgery. The survival of mice was calculated 24 h, 48 h, 72 h, and 96 h after CLP surgery. Two weeks later, open-field test and Morris water maze test were conducted to evaluate the protective effect of atorvastatin. Inflammatory cytokines in plasma, oxidative stress parameters, number of astrocytes, and neuronal cell deaths in the CA3 region of the hippocampus were examined using enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. The results indicate that pretreatment with atorvastatin can increase survival percentage and improve cognitive function. Atorvastatin reversed all these alterations in parallel with a decrease in circulating levels of cytokines (IL-1β, IL-4, IL-6, and TNF-α) in plasma, inhibited the activities of oxidative stress parameters (lower TBARS levels, ratio of GSH/GSSH, and activities of SOD and CAT), enhanced the activity of citrate synthase in brain, and reduced the number of astrocytes and neuronal cell deaths in CA3 region of hippocampus. Overall, our results indicated that atorvastatin exhibited protective effects on survival rate and cognitive disorders after sepsis by inhibiting the release of inflammatory cytokines, oxidative stress, and neuronal apoptosis in brain tissue. [ABSTRACT FROM AUTHOR]

Background: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed.Methods: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations.Results: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which 4 are best practice statements, 9 are strong recommendations, and 35 are weak recommendations. No recommendation was provided for 6 questions. The topics were: (1) infection control, (2) laboratory diagnosis and specimens, (3) hemodynamic support, (4) ventilatory support, and (5) COVID-19 therapy.Conclusion: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new recommendations in further releases of these guidelines. [ABSTRACT FROM AUTHOR]

The prospect of patient harm caused by the decisions made by an artificial intelligence-based clinical tool is something to which current practices of accountability and safety worldwide have not yet adjusted. We focus on two aspects of clinical artificial intelligence used for decision-making: moral accountability for harm to patients; and safety assurance to protect patients against such harm. Artificial intelligence-based tools are challenging the standard clinical practices of assigning blame and assuring safety. Human clinicians and safety engineers have weaker control over the decisions reached by artificial intelligence systems and less knowledge and understanding of precisely how the artificial intelligence systems reach their decisions. We illustrate this analysis by applying it to an example of an artificial intelligence-based system developed for use in the treatment of sepsis. The paper ends with practical suggestions for ways forward to mitigate these concerns. We argue for a need to include artificial intelligence developers and systems safety engineers in our assessments of moral accountability for patient harm. Meanwhile, none of the actors in the model robustly fulfil the traditional conditions of moral accountability for the decisions of an artificial intelligence system. We should therefore update our conceptions of moral accountability in this context. We also need to move from a static to a dynamic model of assurance, accepting that considerations of safety are not fully resolvable during the design of the artificial intelligence system before the system has been deployed. [ABSTRACT FROM AUTHOR]

Rationale: There have been advances in both cancer and sepsis treatment over the past several decades, yet little is known about trends in sepsis-associated mortality in patients with versus without cancer.Objectives: To assess trends in sepsis-associated mortality in hospitalized patients with and without cancer using objective clinical criteria to identify sepsis and detailed clinical data to adjust for severity of illness.Methods: This was a retrospective cohort study at a tertiary referral hospital and cancer center. Adult in-patients with clinical indicators of sepsis (U.S. Centers for Disease Control and Prevention Adult Sepsis Event criteria) were identified between 2003 and 2014. Patients with cancer were identified using diagnosis codes from their hospitalization or the preceding 90 days. Sepsis-associated in-hospital mortality rates were assessed in 3-year intervals. Multivariable logistic regression models were used to adjust for case mix and severity of illness and to test for subgroup interactions in trends.Results: The cohort included 20,975 patients with sepsis, of whom 7,489 (35.7%) had cancer (61.7% solid and 38.3% hematologic). Sepsis-associated mortality rates in patients with cancer decreased from 31.3% in 2003-2005 to 26.0% in 2012-2014 (absolute decrease, 5.2% [95% confidence interval (CI), 2.3-8.2%]). This mortality reduction persisted after risk adjustment (adjusted odds ratio, 0.53 [95% CI, 0.45-0.63] in 2012-2014 relative to 2003-2005). In contrast, sepsis-associated mortality rates increased in patients without cancer from 20.9% in 2003-2005 to 23.9% in 2012-2014 (absolute increase, 2.1% [95% CI, 0.1-4.1%]), but were stable after risk-adjustment (adjusted odds ratio, 0.90 [95% CI, 0.79-1.03]) (P < 0.001 for comparison of trends between patients with vs. without cancer on both crude and adjusted analysis). Among patients with cancer, declines in risk-adjusted sepsis-associated mortality were observed in both solid and hematologic cancer subgroups, with both community-onset and hospital-onset sepsis, in patients receiving active cancer treatments, and in patients requiring mechanical ventilation at sepsis onset.Conclusions: Sepsis-associated mortality rates declined significantly over a 12-year period in patients with cancer, but not in patients without cancer. Potential explanations include advances in the management of cancer and/or better sepsis treatments specifically in patients with cancer. Further research is needed to elucidate the reasons for our findings and to assess their generalizability to other hospitals. [ABSTRACT FROM AUTHOR]

The transition to antibiotic-free poultry production in the face of pathogenic threats is a very challenging task. We recently demonstrated that mucosal delivery of CpG-ODN alone by the intrapulmonary route (IPL) has potential as an effective alternative to antibiotics in neonatal chicks against Escherichia coli septicemia. How exactly mucosal delivery of CpG-ODN elicits, protective antibacterial immunity remained poorly understood. In this study, CpG-ODN or saline was delivered via the intrapulmonary route to day-old chicks (n = 80/group) using a compressor nebulizer in an acrylic chamber (1 mg/mL CpG-ODN for 15 minutes). In the first part of the study, two days after mucosal CpG-ODN delivery, 40 chicks from each group were challenged subcutaneously with 1 × 105 cfu (n = 20) or 1 × 106 cfu (n = 20) of E. coli and the mortality pattern was monitored for seven days. We found significantly higher survival, better clinical conditions and lower bacterial loads in chicks that received mucosal CpG-ODN. To explore the mechanisms behind this protective immunity, we first looked at the kinetics of the cytokine gene expression (three birds/ group/ time for 10 time-points) in the lungs and spleens. Multiplex gene analysis demonstrated a significant elevation of pro-inflammatory cytokine genes mRNA in the CpG-ODN group. Interleukin (IL)-1β robustly upregulated many folds in the lung after CpG-ODN delivery. Lipopolysaccharide-induced tumor necrosis factor (LITAF) and IL-18 showed expression for an extended period in the lungs. Anti-inflammatory cytokine IL-10 was upregulated in both lungs and spleen, whereas IL-4 showed upregulation in the lungs. To investigate the kinetics of immune enrichment in the lungs and spleens, we performed flow cytometry, histology, and immunohistochemistry at 24, 48 and 72 hrs after CpG-ODN delivery. CpG-ODN treated lungs showed a significant enrichment with monocytes/macrophages and CD4+ and CD8+ T-cell subsets. Macrophages in CpG-ODN treated group demonstrated mature phenotypes (higher CD40 and MHCII expression). Importantly, mucosal delivery of CpG-ODN via the intrapulmonary route significantly enriched immune compartment in the spleen as well, suggesting a systemic effect in neonatal chicks. Altogether, intrapulmonary delivery of aerosolized CpG-ODN orchestrates protective immunity against E. coli septicemia by not only enhancing mucosal immunity but also the systemic immune responses. [ABSTRACT FROM AUTHOR]

Background. Sepsis is a global major health problem with high mortality rates. More effective therapy is needed for treating sepsis. Acupuncture has been used for various diseases, including severe infection, in China for more than 2,000 years. Previous studies reported that acupuncture at Zusanli (ST36) might be effective in treating sepsis, but the efficacy and the quality of evidence remain unclear since there is no systematic review on acupuncture at ST36 for sepsis. Methods. Seven databases were searched from the inception of each database up to May 2019. Ultimately, 54 studies using acupuncture at ST36 for the treatment of experimental sepsis were identified in both English and Chinese literature with systematic review procedures. Results. Acupuncture might be useful in reducing injuries induced by sepsis in cardiac, lung, kidney, liver, gastrointestinal tract, and immune system. Its potential mechanisms for antisepsis might include reducing oxidative stress and inflammation, improving microcirculatory disturbance, and maintaining the immune balance mediated by dopamine. However, the positive findings should be interpreted with caution due to poor methodological quality and publication bias. Conclusion. Acupuncture at ST36 might be a promising complementary strategy for controlling sepsis inflammation, yet further studies are needed. [ABSTRACT FROM AUTHOR]

Introduction: Cytokines and granulocyte elastase produced in sepsis cleave a disintegrin and metalloprotease with thrombospondin type I motif 13 (ADAMTS13) and deplete its levels. By this mechanism, sepsis results in microangiopathic hemolytic anemia (MAHA) with thrombocytopenia. Hence, the hypothesis is that plasmapheresis may help in sepsis-induced thrombotic microangiopathy (sTMA), by removing the factors responsible for low levels of ADAMTS13. In tropical countries like India, the contribution of sepsis to intensive care unit (ICU) mortality is high; and hence, it is essential to look out for newer modalities of sepsis treatment. There is abundant literature on the use of plasmapheresis in sepsis but data on its use in sTMA are limited, thus necessitating further research in this field. Case description: This case series studies the outcomes of five patients admitted with sTMA in the ICU and attempts to evaluate the effectiveness of plasmapheresis in improving their outcomes. All patients diagnosed with sTMA and treated with plasmapheresis, between January 2016 and August 2018 at our tertiary care center, were selected for the study. The diagnosis of sepsis was based on sepsis-3 definition. Results: Four different gram-negative organisms were found to have caused MAHA, with the commonest source being either urinary tract infection (UTI) or lower respiratory tract infection. Three of five patients required hemodialysis and two had disseminated intravascular coagulation (DIC). All five had good outcome and recovered well from the acute episode post plasmapheresis. Discussion: In two of five patients, the initial smear was negative and hence the need for repeated examination of the peripheral blood smear should be kept in mind in cases of sTMAs. The median of the number of plasmapheresis sessions required in sTMA is six, which is lesser than that required for primary thrombotic thrombocytopenic purpura (TTP). Hence, the duration of central line placement and the risk of catheter-related complications are low. Based on the observations made in this case study, further exploratory studies are required to evaluate the efficacy of plasmapheresis in sTMA secondary to tropical infections. [ABSTRACT FROM AUTHOR]

BACKGROUND Septic children cause high protein degradation and inadequate nutritional intake would worsen the outcomes. In addition, there are conflicting results of association between tumor necrosis factor-α (TNFA)-308 polymorphism and poorer outcomes. This study was aimed to investigate the impact of high protein feeding in septic children and to examine the role of the TNFA-308 polymorphism in outcome of sepsis. METHODS In this randomized controlled trial, septic children were randomly assigned to receive either high protein feeding (amino acid of 4 g/kg of body weight [kgBW]/ day) or standard nutrient (amino acid of 2 g/kgBW/day) for three days in the pediatric intensive care unit of four hospitals in Indonesia. The patient's enrollment was done between April 2016 and May 2017. The primary outcome was the pediatric logistic organ dysfunction (PELOD) score. TNFA-308 polymorphism was investigated using restriction fragment length polymorphism method in both groups. PELOD score was analyzed as mean differences and gene polymorphism was analyzed with mortality in a subgroup. RESULTS There were 40 children in each group. PELOD score on day-1 (22.4 versus 20.5, p = 0.429), day-2 (20.5 versus 19.8, p = 0.815), and day-3 (18.8 versus 19.8, p = 0.772) were not lower in high protein feeding compared to standard feeding. TNFA-308 polymorphism had no role in mortality of both groups (high protein, p = 0.426; standard, p = 0.456). CONCLUSIONS From this study, researchers concluded that a high protein intervention did not significantly decrease the PELOD score, length of stay, and duration of ventilator use in both groups. [ABSTRACT FROM AUTHOR]

In caring for patients with sepsis, the current structure of electronic health record systems allows clinical providers access to raw patient data without imputation of its significance. There are a wide range of sepsis alerts in clinical care that act as clinical decision support tools to assist in early recognition of sepsis; however, there are serious shortcomings in existing health information technology for alerting providers in a meaningful way. Little work has been done to evaluate and assess existing alerts using implementation and process outcomes associated with health information technology displays, specifically evaluating clinician preference and performance. We developed graphical model displays of two popular sepsis scoring systems, quick Sepsis Related Organ Failure Assessment and Predisposition, Infection, Response, Organ Failure, using human factors principles grounded in user-centered and interaction design. Models will be evaluated in a larger research effort to optimize alert design to improve the collective awareness of high-risk populations and develop a relevant point-of-care clinical decision support system for sepsis. [ABSTRACT FROM AUTHOR]

Objective: To describe the effect of fluid bolus therapy (FBT) on blood pressure in children with sepsis. Secondary outcomes included the effect of FBT on systemic vascular resistance, shock index and shock phenotype (warm or cold). Methods: This was a prospective observational study in the ED of The Royal Children's Hospital, Melbourne, Australia. Participants were children meeting international consensus criteria for sepsis who received FBT for tachycardia or hypotension. FBT was defined as 10–20 mL/kg of 0.9% saline. Mean blood pressure (MBP) was recorded at baseline, 5 and 60 min after FBT. Total systemic vascular resistance index (TSVRi), shock index, and shock phenotype were derived for each time point. Hypotension was defined as MBP <55 + 1.5 × age (years). Warm shock was defined as TSVRi <800 dyne s/cm5/m2. Results: Fifty fluid boluses were recorded in 41 children. Median MBP was 78 mmHg (interquartile range [IQR] 63–86) at baseline, 72 mmHg (IQR 60–82) at 5 min, and 75 mmHg (IQR 66–84) at 60 min. Hypotension was observed in 16% at baseline, 26% at 5 min and 17% at 60 min. Median TSVRi was 1580 dyne s/cm5/m2 (IQR 1242–2206) at baseline, 1254 dyne s/cm5/m2 (IQR 1027–1787) at 5 min, and 1850 dyne s/cm5/m2 (IQR 1265–2140) at 60 min. Median shock index was 1.60 (IQR 1.34–1.90) at baseline, 1.49 (IQR 1.25–1.76) at 5 min and 1.37 (IQR 1.22–1.61) at 60 min. Two percent of cases had warm shock at baseline, 12% at 5 min and 2% at 60 min. Conclusions: MBP initially decreased following FBT for paediatric sepsis, returning towards baseline over the subsequent 60 min. The utility of FBT for increasing MBP and its effect on patient‐centred outcomes in children with sepsis warrants further exploration. [ABSTRACT FROM AUTHOR]

Sepsis is a significant cause of morbidity and mortality worldwide. Early diagnosis and management of sepsis is critical to improving patient prognoses. Surviving sepsis campaign guidelines issued in 2016 encourage health institutions to establish a screening system to identify patients who are at risk of sepsis. In 2012, the Royal College of Physicians in the UK began to advocate replacing local and regional scoring systems with the National Early Warning Score (NEWS), which is optimized for the identification of sepsis. Although many hospitals continue to use other scoring systems, all healthcare organizations are being encouraged to adopt a standardized scoring system to better promote patient safety by facilitating rapid diagnoses and screenings and thus, subsequently, improving decisionmaking by clinical staffs. NEWS plays a very important role in the treatment of sepsis patients. Although research findings related to this scoring system differ somewhat, they provide an important reference for clinical nursing staffs. Intelligent systems are not comprehensive in terms of their capabilities. However, combining human intelligence with system features and further optimizing the system should contribute significantly to the reduction of mortality risk in patients with sepsis. [ABSTRACT FROM AUTHOR]

Neonatal sepsis is characterised by dysregulated immune responses. Lipid mediators (LMs) are involved in the regulation of inflammation. Human recombinant thrombomodulin (rhTM), an anticoagulant, has anti-inflammatory effects and might be useful for sepsis treatment. A stock caecal slurry (CS) solution was prepared from adult caeca. To induce sepsis, 1.5 mg/g of CS was administered intraperitoneally to 4 d-old wild-type FVB mouse pups. Saline (Veh-CS) or rhTM (3 or 10 mg/kg; rhTM3-CS or rhTM10-CS) was administered subcutaneously 6 h prior to sepsis induction, and liver LM profiles at 3 and 6 h post-sepsis induction and survival up to 7 days were examined. Mortality was significantly lower (47%) in the rhTM3-CS group and significantly higher (100%) in the rhTM10-CS group, compared with the Veh-CS group (79%, p < 0.05). Eleven LMs (12-HEPE, EPA, 14-HDHA, DHA, PD1, PGD2, 15d-PGJ2, 12S-HHT, lipoxin B4, 12-HETE, AA) were significantly increased at 3 h, and five LMs (5-HEPE, 15-HEPE, 18-HEPE, 17-HDHA, PD1) were significantly increased at 6 h post-sepsis induction. Increased EPA, DHA, 12S-HHT, lipoxin B4, and AA were significantly suppressed by rhTM pre-treatment. rhTM was protective against neonatal sepsis. This protective effect might be mediated via LM modulation. Further post-sepsis studies are needed to determine clinical plausibility. [ABSTRACT FROM AUTHOR]

Objective: Sepsis-induced immune alterations are associated with secondary infections and increased risk of death. The use of mesenchymal stem cells (MSCs) has been described as a novel therapeutic strategy. We evaluated the immunomodulatory effects of human dental follicle (DF-MSCs) on lymphocytes of sepsis and septic shock patients. Materials and Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood samples of sepsis, septic shock and healthy subjects. PBMCs were co-cultured in the presence and absence of DF-MSCs with or without interferon-gamma (IFN-γ) for 72 hours. CD4+CD25+FoxP3+regulatory T (Treg) cell frequency, lymphocyte proliferation, cytokine levels and apoptosis were evaluated via flow cytometry. Results: DF-MSCs significantly suppressed proliferation of lymphocytes in sepsis group compared to septic shock group (p<0.005). DF-MSCs remarkably increased Treg ratio in sepsis compared to control group (p<0.05). Reduction of lymphocyte apoptosis in co-cultures of DF-MSCs and PBMC was significant in both sepsis and septic shock groups. IFN-γ stimulation of DF-MSCs ameliorated shift in the T-cell subsets from Th2 to Th1 phenotype in septic shock. Conclusion: Our findings revealed that DF-MSCs have immunoregulatory effects both in sepsis and septic shock, by reducing interleukin-4 (IL-4) and increasing IFN-γ levels. This immunoreactivity regulation may open new therapeutic approaches for septic shock patients. [ABSTRACT FROM AUTHOR]

Key content: Sepsis is a leading cause of maternal morbidity and mortality, globally and in the UK.In pregnancy and the puerperium, women may be more susceptible to rapid deterioration of illness following an infection.Sepsis has a complex pathophysiology and the immunological and cardiovascular adaptations of normal pregnancy may have an adverse impact on the maternal response to infection. Furthermore, physiological changes of pregnancy, which mimic those of sepsis, often delay recognition and optimal management.'Bedside' identification of pathogens and their antibiotic resistance patterns may help to improve clinical outcomes.Recent updates in sepsis management, areas of controversy and the importance of translational research and clinical trials for pregnancy and the puerperium are discussed. Learning objectives: To highlight the difficulties of diagnosing sepsis in pregnancy.To highlight recent updates, new definitions and controversies of current sepsis management.To highlight the potential for research to develop novel biomarkers and therapeutic agents specific to the pregnant woman. Ethical issues: Sepsis research involving new technologies differentially benefits high‐income countries compared with low‐/middle‐income countries despite the greatest burden of maternal sepsis being in the latter.With the current rapid evolution of omic technology platforms, greater affordability will provide greater accessibility. [ABSTRACT FROM AUTHOR]

In the emergency department (ED) setting, nurses perform the initial evaluation of patients, thereby placing ED nurses in a prime position to recognize sepsis and greatly influence prompt implementation of treatment. The quick Sequential Organ Failure Assessment (qSOFA) tool was first introduced as part of the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) as a predictor of both increased mortality and longer intensive care unit (ICU) stays. Designed for use outside the ICU, the qSOFA tool functions as a simple bedside tool to quickly identify patients at risk for developing sepsis. As a method to improve detection of sepsis in the ED, an evidence-based screening tool based on the qSOFA criteria was developed. The project implemented over a 14-day period resulted in 106 surveys. Average time from patients entering the ED to actual triage evaluation was 13 min, and the median time from the completion of triage evaluation to the completion of the qSOFA screening tool was 4 min. To determine acceptance of the qSOFA tool for use in detecting sepsis in the ED, a second aim was to evaluate ED nurses' perceptions of the effectiveness, timeliness, and ease of use of the qSOFA evaluation tool. Anonymous postsurvey results revealed that participants were moderately familiar with the qSOFA tool and found it overall easy to complete. The majority of participants stated only a slight likelihood of using the qSOFA tool if it were implemented into clinical practice. [ABSTRACT FROM AUTHOR]

Sepsis, severe sepsis, and septic shock represent progression of a single illness associated with high morbidity, mortality, and cost. This project emphasized the importance of providing medicalsurgical nurses with education on early recognition of sepsis to improve goal-directed therapy times. [ABSTRACT FROM AUTHOR]

The article presents information on treatment of Sepsis in the U.S. Topics include perform retrospective cohort study of several medicare beneficiaries hospitalized for sepsis by use of medicare claims for hospitalization and postacute care discharge; diagnosis related groups (DRG) are selected to identify sepsis for payment purposes; and analyses discharge disposition by mechanical ventilation and admission to the intensive care unit (ICU).

Protein-energy malnutrition (PEM), resulting from depleted energy and nutrient stores, compromises the body's defense systems and may exacerbate sepsis and its impact. However, population-based studies examining the association of PEM on the prevalence and health-care burden of sepsis are lacking. To investigate the relationship between PEM and sepsis, influence of PEM on clinical outcomes of sepsis, and impact of PEM on trends in sepsis mortality. The primary study is a retrospective cohort analysis of the 2012-2014 National Inpatient Sample (NIS) patient discharge records. Secondary analyses are cross-sectional study on the 2014 NIS and trend analysis on 2007-2014 NIS. The primary study included adult inpatient hospitalizations for sepsis in the United States. Mortality, complicated sepsis, and 10 other metrics of clinical outcomes and health care utilization. First, patients with sepsis (2014 NIS) were stratified into two groups: uncomplicated (without shock) and complicated (with shock). The adjusted odds ratio of having sepsis (total, uncomplicated, and complicated) was estimated with PEM as predictor using logistic regressions (binomial and multinomial). Second, among patients with sepsis (2012-2014 NIS), PEM cases were matched to cases without PEM (no-PEM) using a greedy-algorithm based propensity-matching methodology (1:1), and the outcomes were measured with conditional regression models. Finally, the trend in mortality from sepsis was calculated, stratified by PEM status, as an effect modifier, using Poisson models (2007-2014 NIS). All models accounted for the complex sampling methodology (SAS 9.4). In 2014, PEM was associated with higher odds for sepsis (3.97 [3.89 to 4.05], P <0.0001) and complicated vs uncomplicated sepsis (1.74 [1.67 to 1.81], P <0.0001). From 2012-2014, about 18% (167,133 of 908,552) of hospitalizations for sepsis had coexisting PEM. After propensity matching, PEM was associated with higher mortality (adjusted odds ratio: 1.35 [1.32 to 1.37], P <0.0001), cost ($160,724 [159,517 to 161,940] vs $86,650 [85,931 to 87,375], P <0.0001), length of stay (14.8 [14.9 to 14.8] vs 8.5 [8.5 to 8.6] days, P <0.0001), adverse events, and resource utilization. Although mortality in sepsis has been trending down from 2007-2014 (−1.19% per year, P trend<0.0001), the decrease was less pronounced among those with PEM vs no-PEM (−0.86% per year vs −1.29% per year, P <0.0001). PEM is a risk factor for sepsis and associated with poorer outcomes among patients with sepsis. A concerted effort involving all health care workers in the prevention, identification, and treatment of PEM in community-dwelling people before hospitalization might mitigate against these devastating outcomes. [ABSTRACT FROM AUTHOR]

Pediatric sepsis is a major public health concern, and robust surveillance tools are needed to characterize its incidence, outcomes, and trends. The increasing use of electronic health records (EHRs) in the United States creates an opportunity to conduct reliable, pragmatic, and generalizable population-level surveillance using routinely collected clinical data rather than administrative claims or resource-intensive chart review. In 2015, the US Centers for Disease Control and Prevention recruited sepsis investigators and representatives of key professional societies to develop an approach to adult sepsis surveillance using clinical data recorded in EHRs. This led to the creation of the adult sepsis event definition, which was used to estimate the national burden of sepsis in adults and has been adapted into a tool kit to facilitate widespread implementation by hospitals. In July 2018, the Centers for Disease Control and Prevention convened a new multidisciplinary pediatric working group to tailor an EHR-based national sepsis surveillance approach to infants and children. Here, we describe the challenges specific to pediatric sepsis surveillance, including evolving clinical definitions of sepsis, accommodation of agedependent physiologic differences, identifying appropriate EHR markers of infection and organ dysfunction among infants and children, and the need to account for children with medical complexity and the growing regionalization of pediatric care. We propose a preliminary pediatric sepsis event surveillance definition and outline next steps for refining and validating these criteria so that they may be used to estimate the national burden of pediatric sepsis and support site-specific surveillance to complement ongoing initiatives to improve sepsis prevention, recognition, and treatment. [ABSTRACT FROM AUTHOR]

Sepsis is a common diagnosis with a high mortality and is a leading cause of in-hospital death. Sepsis manifests in increasing severity along a continuum that begins with systemic inflammatory response syndrome, and progresses to sepsis, septic shock, and multiple organ dysfunction syndrome. During their careers, all critical care nurses will likely care for patients experiencing sepsis. However, this is a challenging task, as treatment modalities and guidelines change in response to our evolving understanding of this complex disorder. To provide quality care in the face of these changes, it is imperative that critical care nurses have a solid understanding of the complex pathophysiology of sepsis. In this article, a unique framework for simplifying, understanding, and recalling the pathophysiology of sepsis is presented as the "ABCCs of sepsis", and the impact of this pathophysiology on a patient's cellular oxygen supply and demand balance is described. The links between the pathophysiology and the patient's overall clinical presentation and consequent treatment are clarified. The ABCCs framework supports nurses in understanding the pathophysiology of sepsis, and the rationale behind treatment protocols. This, in turn, promotes effective clinical decision-making during provision of both medical and nursing care. The ABCCs framework can also be used as a teaching tool by critical care nurse educators to help nurses understand this complex and serious syndrome. [ABSTRACT FROM AUTHOR]

Fluid resuscitation, to restore intravascular volume and improve oxygen delivery, is a crucial step in early resuscitation efforts of patients with sepsis or septic shock. The 2016 Surviving Sepsis Campaign guidelines suggest the use of dynamic versus static measures of fluid responsiveness and fluid resuscitation with at least 30 mL/kg of intravenous crystalloid within the first 3 hours followed by fluid administration if hemodynamic factors continue to improve. Despite these recommendations, risks to this practice may exist as multiple studies have demonstrated an association between a positive fluid balance and/or administration of large fluid volume and increase in mortality. These studies are limited by variations in their methodologic design; therefore, cause and effect cannot yet be determined. Future multicenter, randomized, controlled studies that evaluate fluid balance and fluid volume need to be conducted to clarify the role of fluid administration to patients with sepsis to maximize benefits and minimize risk. [ABSTRACT FROM AUTHOR]

Background Hospitalist medicine was predicated on the belief that providers dedicated to inpatient care would deliver higher quality and more cost-effective care to acutely hospitalised patients. The literature shows mixed results and has identified care variation as a culprit for suboptimal quality and cost outcomes. Using a scientifically validated engagement and measurement approach such as Clinical Performance and Value (CPV), simulated patient vignettes may provide the impetus to change provider behaviour, improve system cohesion, and improve quality and cost efficiency for hospitalists. Methods We engaged 33 hospitalists from four disparate hospitalist groups practising at Penn Medicine Princeton Health. Over 16 months and four engagement rounds, participants cared for two patients per round (with a diagnosis of chronic obstructive pulmonary disease [COPD] and sepsis), then received feedback, followed by a group discussion. At project end, we evaluated both simulated and real-world data to measure changes in clinical practice and patient outcomes. Results Participants significantly improved their evidence-based practice (+13.7% points, p<0.001) while simultaneously reducing their variation (-1.4% points, p=0.018), as measured by the overall CPV score. Correct primary diagnosis increased significantly for both sepsis (+19.1% points, p=0.004) and COPD (+22.7% points, p=0.001), as did adherence to the sepsis 3-hour bundle (+33.7% points, p=0.010) and correct admission levels for COPD (+26.0% points, p=0.042). These CPV changes coincided with real-world improvements in length of stay and mortality, along with a calculated $5 million in system-wide savings for both disease conditions. Conclusion This study shows that an engagement system--using simulated patients, benchmarking and feedback to drive provider behavioural change and group cohesion, using parallel tracking of hospital data--can lead to significant improvements in patient outcomes and health system savings for hospitalists. [ABSTRACT FROM AUTHOR]

Sepsis is the primary cause of acute kidney injury in critically ill patients. During the past decades, several extracorporeal blood purification techniques have been developed for sepsis and sepsis-induced acute kidney injury management. These therapies could act on both the infectious agent itself and the host immune response. In this article, we review the available literature discussing the different extracorporeal blood purification techniques, including high-volume hemofiltration, cascade hemofiltration, hemoperfusion, coupled plasma filtration adsorption, plasma exchange, and specific optimized renal replacement therapy membranes. [ABSTRACT FROM AUTHOR]

Purpose: The Centers for Medicare and Medicaid Services (CMS) and the American College of Emergency Physicians (ACEP) developed national quality measures for emergency department (ED) sepsis care. Like care for many conditions, meeting sepsis quality metrics can vary between settings. We sought to examine and compare sepsis care quality in rural vs urban hospital‐based EDs. Methods: We analyzed data from EDs participating in the national Emergency Quality Network (E‐QUAL). We collected preliminary performance data on both the CMS measure (SEP‐1) and the ACEP measures via manual chart review. We analyzed SEP‐1 data at the hospital level based on existing CMS definitions and analyzed ACEP measure data at the patient level. We report descriptive statistics of performance variation in rural and urban EDs. Findings: Rural EDs comprised 58 of the EDs reporting SEP‐1 results and 405 rural patient charts in the manual review. Of sites reporting SEP‐1 results, 44% were rural and demonstrated better aggregate SEP‐1 bundle adherence than urban EDs (79% vs 71%; P = .049). Both urban and rural hospitals reported high levels of compliance with the ACEP recommended initial actions of obtaining lactate and blood cultures, with urban EDs outperforming rural EDs on metrics of IV fluid administration and antibiotics (74% urban vs 60% rural; P ≤ .001; 91% urban vs 84% rural; P ≤ .001, respectively). Conclusions: Sepsis care at both rural and urban EDs often achieves success with national metrics. However, performance on individual components of ED sepsis care demonstrates opportunities for improved processes of care at rural EDs. [ABSTRACT FROM AUTHOR]

Copyright of Enfermagem Brasil is the property of Atlantica Editora and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: The purpose of this study was to examine potential gender disparities in relation to factors associated with sepsis management among a cohort of patients admitted through an emergency department with a discharge diagnosis of severe sepsis or septic shock. Sepsis is one of the leading causes of death globally, with significant associated costs. Predictors of survival for those with sepsis‐related diagnoses are complex. Design and Methods: The study had a retrospective, descriptive cross‐sectional design. The sample (N = 482) included patients 18 years of age or older who presented to the emergency department of a nonprofit, Magnet‐recognized, acute care hospital located in southern California. Subjects included those who subsequently met the criteria for a discharge diagnosis of severe sepsis or septic shock as defined by the Surviving Sepsis Campaign. Patient characteristics, clinical variables, care management processes, and outcomes were extracted from the electronic health record. A multivariate model was analyzed. Findings: The sample included 234 women (48.5%) and 248 men (51.5%). Logistic regression with eight independent variables (discharge diagnosis, age, comorbidities, length of hospital stay, source of infection, first serum lactate level measured, recommended fluids administered, and gender) reliably predicted odds for patient survival, ϰ2 (12) = 118.38, p <.001, and correctly classified 77.3% of cases. All eight independent variables significantly contributed to the model. Men had a higher likelihood of hospital survival than women (odds ratio 1.68; 95% confidence interval 1.01–2.79; p =.045). Conclusions: The Surviving Sepsis Campaign has provided a clear pathway for care of patients with sepsis‐related diagnoses. Therapeutic strategies should be developed to address differences in outcome by gender. The adoption of more aggressive applications of evidence‐based interventions for these patients may result in better patient outcomes. Clinical Relevance: Providers should understand the importance of adhering to sepsis protocols, minimizing treatment disparities, and recognizing gender differences. [ABSTRACT FROM AUTHOR]

Sepsis continues to be a leading public health burden in the United States and worldwide. With the increasing use of advanced laboratory technology, there is a renewed interest in the use of biomarkers in sepsis to aid in more precise and targeted decision-making. Natriuretic peptides have been increasingly recognized to play a role outside of heart failure. They are commonly elevated among critically ill patients in the setting of cardiopulmonary dysfunction and may play a role in identifying patients with sepsis and septic shock. There are limited data on the role of these biomarkers in the diagnosis, management, outcomes and prognosis of septic patients. This review seeks to describe the role of natriuretic peptides in fluid resuscitation, diagnosis of ventricular dysfunction and outcomes and the prognosis of patients with sepsis. B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) have been noted to be associated with left ventricular systolic and diastolic and right ventricular dysfunction in patients with septic cardiomyopathy. BNP/NT-proBNP may predict fluid responsiveness, and trends of these peptides may play a role in fluid resuscitation. Despite suggestions of a correlation with mortality, the role of BNP in mortality outcomes and prognosis during sepsis needs further evaluation. [ABSTRACT FROM AUTHOR]

Much of the activity in critical care is complex but repetitive. In order to standardize care and maintain safety, delivery of care is often directed by protocols and care bundles. This case study will reflect on an instance where care transcended the standard protocol‐directed path to be more individualized, creative and compassionate. Acts like these can be unique for the practitioners involved and require an element of positive risk taking, which happened here. It will look at the decision‐making, planning and risk involved in preparing for a terminally ill patient, who was inotrope and high‐flow oxygen dependent, to go home to have treatment withdrawn there instead of in the hospital. This was to fulfil his wish to die at home. In unpicking the circumstances where this positive risk taking led to the desired outcome and the relationship between safety, uncertainty and risk, three themes arose. These were the journey to safe uncertainty; decision‐making with uncertain outcomes; and the importance of robust human factors, particularly effective communication and inter‐professional teamwork. If positive risk taking can result in enhanced outcomes for the patient, then the question of how this behaviour can be fostered and encouraged must be addressed. [ABSTRACT FROM AUTHOR]

After 2013, when New York State mandated that hospitals follow protocols to treat sepsis, completion of the protocols increased and mortality declined. Whether these encouraging trends have equitably benefited racial/ethnic minority populations is unknown. Although there were no significant racial/ethnic differences in rates of protocol completion at the onset of New York's Sepsis Initiative, over time white patients experienced a greater increase in protocol completion rates (14.0 percentage points) compared to black patients (5.3 percentage points). The emergence of this disparity was due to smaller performance improvements among hospitals with higher proportions of black patients, though white and black patients showed similar improvements when treated within the same hospital. Our study suggests an urgent need to understand why improvements in sepsis care lagged in hospitals in New York that care for higher proportions of minority patients. Policy makers should anticipate and monitor the effects of quality improvement initiatives on disparities to ensure that all racial/ethnic groups realize their benefits equitably. [ABSTRACT FROM AUTHOR]

Objectives: It is unclear if a low- or high-volume IV fluid resuscitation strategy is better for patients with severe sepsis and septic shock.Design: Prospective randomized controlled trial.Setting: Two adult acute care hospitals within a single academic system.Patients: Patients with severe sepsis and septic shock admitted from the emergency department to the ICU from November 2016 to February 2018.Interventions: Patients were randomly assigned to a restrictive IV fluid resuscitation strategy (≤ 60 mL/kg of IV fluid) or usual care for the first 72 hours of care.Measurements and Main Results: We enrolled 109 patients, of whom 55 were assigned to the restrictive resuscitation group and 54 to the usual care group. The restrictive group received significantly less resuscitative IV fluid than the usual care group (47.1 vs 61.1 mL/kg; p = 0.01) over 72 hours. By 30 days, there were 12 deaths (21.8%) in the restrictive group and 12 deaths (22.2%) in the usual care group (odds ratio, 1.02; 95% CI, 0.41-2.53). There were no differences between groups in the rate of new organ failure, hospital or ICU length of stay, or serious adverse events.Conclusions: This pilot study demonstrates that a restrictive resuscitation strategy can successfully reduce the amount of IV fluid administered to patients with severe sepsis and septic shock compared with usual care. Although limited by the sample size, we observed no increase in mortality, organ failure, or adverse events. These findings further support that a restrictive IV fluid strategy should be explored in a larger multicenter trial. [ABSTRACT FROM AUTHOR]

Objective: To provide a record of the implementation and outcome of surviving sepsis campaign 2016 at Dr. Soetomo General Hospital, Surabaya, Indonesia, such as 3- and 6-hour sepsis bundle compliance as a baseline and the Sepsis- related Organ Failure Assessment (SOFA) score after 48 hours of treatment. SOFA values were used to predict mortality in the hospital. Design: This was an observational experimental study that used cross sectional design. Setting: Resuscitation room in Dr. Soetomo General Hospital. Patients and participants: A purposive sample was taken of patients older than 17-year-old suspected with sepsis or septic shock according to diagnosis criteria from Surviving Sepsis Campaign (SSC) 2016. Thirty-two patients, consist of 24 male and 8 female patients were included. Interventions: After patients were suspected of sepsis or septic shock according to diagnosis criteria from SSC 2016, they were treated with 3- and 6-hour sepsis bundle, then the data were collected with questionnaire. Measurements and results: We found 75% of patients received a 3-hour sepsis bundle in <3 hours, and 50% of patients had 6-hour sepsis bundle in <6 hours. The compliance rate of 3- and 6-hour sepsis and septic shock bundles reached 46.88%. SOFA scores before and after 48-hour management of sepsis had a significant increase with p=0.001 (p<0.05). Conclusions: There were significant decreasing of SOFA values in baseline and 48 hours after the management of sepsis and septic shock in 81.25% patients (n=26). This result suggests that management of sepsis based on SSC 2016 contribute to the improvement of the patient's condition and better prognosis. [ABSTRACT FROM AUTHOR]

Every year, sepsis affects nearly 30 million people worldwide, with current annual estimates reporting as many as 6 million deaths. To combat the staggering number of patients who are affected by sepsis, clinicians continue to investigate novel treatment approaches. One treatment approach that has gained interest is the role that vitamins and nutrients play in the body's response to sepsis. Thiamine, in particular, has been studied because of its role in glucose metabolism and lactate production. This review provides a summary of the current literature surrounding the use of thiamine in the treatment of sepsis and describes the function of this essential nutrient in sepsis pathology. We also aim to provide clinicians with the necessary understanding to recognize the potential for thiamine deficiency, as well as detail the role of thiamine supplementation in the treatment of sepsis. [ABSTRACT FROM AUTHOR]

Among critically ill adults, sepsis remains both common and lethal. In addition to antibiotics and source control, fluid resuscitation is a fundamental sepsis therapy. The physiology of fluid resuscitation for sepsis, however, is complex. A landmark trial found early goal-directed sepsis resuscitation reduced mortality, but 3 recent multicenter trials did not confirm this benefit. Multiple trials in resource-limited settings have found increased mortality with early fluid bolus administration in sepsis, and the optimal approach to early sepsis resuscitation across settings remains unknown. After initial resuscitation, excessive fluid administration may contribute to edema and organ dysfunction. Using dynamic variables such as passive leg raise testing can predict a patient's hemodynamic response to fluid administration better than static variables such as central venous pressure. Whether using measures of "fluid responsiveness" to guide fluid administration improves patient outcomes, however, remains unknown. New evidence suggests improved patient outcomes with the use of balanced crystalloids compared to saline in sepsis. Albumin may be beneficial in septic shock, but other colloids such as starches, dextrans, and gelatins appear to increase the risk of death and acute kidney injury. For the clinician caring for patients with sepsis today, the initial administration of 20 mL/kg of intravenous balanced crystalloid, followed by consideration of the risks and benefits of subsequent fluid administration represents a reasonable approach. Additional research is urgently needed to define the optimal dose, rate, and composition of intravenous fluid during the management of patients with sepsis and septic shock. [ABSTRACT FROM AUTHOR]

The article presents the author's views on the need of extracorporeal blood purification for sepsis and septic shock. It is opined that a safe and effective extracorporeal blood purification device is urgently needed as there is a lack of efficacious drugs for the treatment of these life-threatening conditions. It is stated that the extremely high mortality rate of severe sepsis and septic shock patients is absolutely not acceptable.

Copyright of Nővér is the property of Chamber of Hungarian Health Care Professionals and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To characterize resource availability from a nationally representative random sample of intensive care units in Brazil. Methods: A structured online survey of participating units in the Sepsis PREvalence Assessment Database (SPREAD) study, a nationwide 1-day point prevalence survey to assess the burden of sepsis in Brazil, was sent to the medical director of each unit. Results: A representative sample of 277 of the 317 invited units responded to the resources survey. Most of the hospitals had fewer than 500 beds (94.6%) with a median of 14 beds in the intensive care unit. Providing care for public-insured patients was the main source of income in two-thirds of the surveyed units. Own microbiology laboratory was not available for 26.8% of the surveyed intensive care units, and 10.5% did not always have access to blood cultures. Broad spectrum antibiotics were not always available in 10.5% of surveyed units, and 21.3% could not always measure lactate within three hours. Those institutions with a high resource availability (158 units, 57%) were usually larger and preferentially served patients from the private health system compared to institutions without high resource availability. Otherwise, those without high resource availability did not always have broad-spectrum antibiotics (24.4%), vasopressors (4.2%) or crystalloids (7.6%). Conclusion: Our study indicates that a relevant number of units cannot perform basic monitoring and therapeutic interventions in septic patients. Our results highlight major opportunities for improvement to adhere to simple but effective interventions in Brazil. [ABSTRACT FROM AUTHOR]

Background and Objectives: Mesenchymal stem cells (MSCs)‐based regenerative therapy is now considered as an alternative approach to revive infectious diseases, including sepsis. Nevertheless, the efficiency of MSC application is limited by the poor survival rate of engrafted MSCs. Hence, preconditioning was established as a strategy to increase the cells' efficiency. Methods: MSCs were preconditioned with 1 μg/ml of three different lipopolysaccharides (LPSs) of Pseudomonas (Pse‐LPS), Acinetobacter (Ac‐LPS), and Acinetobacter inactivated lipid A by PagL (Ac‐LPS‐PagL). Then, preconditioned MSCs were exposed to oxidative stress and serum deprivation followed by evaluation of the antibacterial activity, survival, and apoptosis of MSCs. Then, the murine sepsis model treated with 100 μl phosphate‐buffered saline (control group, sepsis group), 100 μl of 1 × 10 6 wild MSCs (MSC group), and three remained groups received 100 μl of 1 × 10 6 LPS‐preconditioned MSCs (Pse‐LPS‐MSCs group: LPS purified from Pseudomonas, or Ac‐LPS‐MSCs group: LPS purified from Acinetobacter, and Ac‐PagL‐LPS‐MSCs group: detoxified LPS Pagl). Results: After 4 days, LPS‐preconditioned MSC transplantation modulated the immune response and reduced inflammation in septic mice. Apoptosis of Pse‐LPS/Ac‐LPS‐preconditioned‐MSCs was obviously reduced in vitro, and the survival rate of engrafted mice was evidently elevated in Pse‐LPS‐MSCs and Ac‐LPS‐MSCs groups compared with other three groups. Conclusion: LPS preconditioning provides an innovative strategy for evolving functional and biological properties of MSCs and ameliorates the survival rate of the mouse model of sepsis after MSC transplantation, protects cells from apoptosis and organ damages, and evaluates therapeutic properties, including immunemodulatory. Mesenchymal stem cells (MSCs)‐based regenerative therapy is now considered as an alternative approach to revive infectious diseases, including sepsis. In our study, lipopolysaccharides (LPS) preconditioning provides an innovative strategy for evolving functional and biological properties of MSCs and ameliorates the survival rate of the mouse model of sepsis after MSC transplantation, protects cells from apoptosis and organ damages, and evaluates therapeutic properties, including immunemodulatory. [ABSTRACT FROM AUTHOR]

Background: Perioperative infection and sepsis are of fundamental concern to perioperative clinicians. However, standardised endpoints are either poorly defined or not routinely implemented. The Standardised Endpoints in Perioperative Medicine (StEP) initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials.Methods: We undertook a systematic review to identify measures of infection and sepsis used in the perioperative literature. A multi-round Delphi consensus process that included more than 60 clinician researchers was then used to refine a recommended list of outcome measures.Results: A literature search yielded 1857 titles of which 255 met inclusion criteria for endpoint extraction. A long list of endpoints, with definitions and timescales, was generated and those potentially relevant to infection and sepsis circulated to the theme subgroup and then the wider StEP-COMPAC working group, undergoing a three-stage Delphi process. The response rates for Delphi rounds 1, 3, and 3 were 89% (n=8), 67% (n=62), and 80% (n=8), respectively. A set of 13 endpoints including fever, surgical site, and organ-specific infections as defined by the US Centres for Disease Control and Sepsis-3 are proposed for future use.Conclusions: We defined a consensus list of standardised endpoints related to infection and sepsis for perioperative trials using an established and rigorous approach. Each endpoint was evaluated with respect to validity, reliability, feasibility, and patient centredness. One or more of these should be considered for inclusion in future perioperative clinical trials assessing infection, sepsis, or both, thereby permitting synthesis and comparison of future results. [ABSTRACT FROM AUTHOR]

Sepsis is a rapidly progressing, life threatening immune response triggered by infection that affects millions worldwide each year. Current clinical diagnosis relies on broad physiological parameters and time consuming lab-based cell culture. If proper treatment is not provided, cases of sepsis can drastically increase in severity over the course of a few hours. Development of new point of care tools for sepsis has the potential to improve diagnostic speed and accuracy, leading to prompt administration of appropriate therapeutics, thereby reducing healthcare costs and improving patient outcomes. In this review we examine developing and commercially available technologies to assess the feasibility of rapid, accurate sepsis diagnosis, with emphasis on point of care. [ABSTRACT FROM AUTHOR]

Increasedmortality has been identified as the sepsis cascade progresses fromsepsis to severe sepsis to septic shock. Estimates reflect sepsis death rates ranging from 10% to 20%, severe sepsis death rates of 20% to 50%, and septic shock fatality rates of 40% to 80%. The high rates of morbidity, mortality, and Medicare costs prompted the Centers for Medicare and Medicaid Services to implement bundled care and public reporting of the Early Management Bundle, Severe Sepsis/Septic Shock (SEP-1) quality measure in 2015. Sepsis care bundles were identified to be beneficial since the 1990s as the bundle facilitates efficient, effective, and timely delivery of care to support quality improvement. The SEP-1measure can be challenging and requires the nurse's active participation. Nurses need increased knowledge of the sepsis cascade and treatments as defined in the SEP-1 quality measure. Increased knowledge and application of bundle elements are lifesaving and can influence postdischarge outcomes. This article discusses the nurse's role inmeeting the specific elements of each bundle and strategies to improve bundle compliance. [ABSTRACT FROM AUTHOR]

Highlights • Sepsis is a common and life-threatening syndrome, and a leading cause of morbidity and mortality globally. • We performed a meta-analysis of observational studies to quantify the performance of a machine learning model to predict sepsis. • For machine learning models, the pooled area under receiving operating curve (SAUROC) for predicting sepsis onset 3 to 4 h before, was 0.89 (95%CI: 0.86–0.92); sensitivity 0.81 (95%CI:0.80–0.81), and specificity 0.72 (95%CI:0.72–0.72). Abstract Study objective Sepsis is a common and major health crisis in hospitals globally. An innovative and feasible tool for predicting sepsis remains elusive. However, early and accurate prediction of sepsis could help physicians with proper treatments and minimize the diagnostic uncertainty. Machine learning models could help to identify potential clinical variables and provide higher performance than existing traditional low-performance models. We therefore performed a meta-analysis of observational studies to quantify the performance of a machine learning model to predict sepsis. Methods A comprehensive literature search was conducted through the electronic database (e.g. PubMed, Scopus, Google Scholar, EMBASE, etc.) between January 1, 2000, and March 1, 2018. All the studies published in English and reporting the sepsis prediction using machine learning algorithms were considered in this study. Two authors independently extracted valuable information from the included studies. Inclusion and exclusion of studies were based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Results A total of 7 out of 135 studies met all of our inclusion criteria. For machine learning models, the pooled area under receiving operating curve (SAUROC) for predicting sepsis onset 3 to 4 h before, was 0.89 (95%CI: 0.86–0.92); sensitivity 0.81 (95%CI:0.80–0.81), and specificity 0.72 (95%CI:0.72–0.72) whereas the pooled SAUROC for SIRS, MEWS, and SOFA was 0.70, 0.50, and 0.78. Additionally, diagnostic odd ratio for machine learning, SIRS, MEWS, and SOFA was 15.17 (95%CI: 9.51–24.20), 3.23 (95%CI: 1.52–6.87), 31.99 (95% CI: 1.54–666.74), and 3.75(95%CI: 2.06–6.83). Conclusion Our study findings suggest that the machine learning approach had a better performance than the existing sepsis scoring systems in predicting sepsis. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide (LPS) sensing in the cytosol by the noncanonical inflammasome leads to pyroptosis and NLRP3 inflammasome activation. This mechanism may be more critical for sepsis development than recognition of LPS by Toll-like receptor 4. LPS is directly binding to its intracellular receptor caspase-4/5/11, mediated by outer membrane vesicles and guanylate-binding proteins that deliver LPS to the cytosol and mediate access of caspases to LPS. Caspase-11-dependent cleavage of gasdermin D is discussed as a link between LPS-induced activation of caspases and pyroptosis or NLRP3 inflammasome activation. Finally, we highlight recently described inhibitors of cytosolic LPS-triggered noncanonical inflammasome activation that might be considered as potential drugs for the treatment of sepsis. Highlights Mouse caspase-11 and human caspase-4/5 recognize Gram-negative bacterial infections and trigger pyroptosis and subsequently NLRP3 inflammasome activation. Cytosolic LPS-mediated pyroptosis, which is triggered by caspase-11 activation independently of TLR4, is a major driver for septic shock. Outer membrane vesicles and host guanylate binding proteins mediate or promote LPS access to the cytosol to activate caspases. Caspase-11-dependent cleavage of gasdermin D and subsequent pore formation link LPS-induced activation of caspases to pyroptosis and NLRP3 inflammasome activation. Targeting noncanonical inflammasome activation by cytosolic LPS may be effective for the clinical treatment of sepsis and septic shock. [ABSTRACT FROM AUTHOR]

Massive apoptosis of lymphocytes is a hallmark of sepsis. The resulting immunosuppression is associated with secondary infections, which are often lethal. Moreover, sepsis-survivors are burdened with increased morbidity and mortality for several years after the sepsis episode. The duration and clinical consequences of sepsis induced-immunosuppression are currently unknown. We have used the mouse model of peritoneal contamination and infection (PCI) to investigate the quantitative and qualitative recovery of T lymphocytes for 3.5 months after sepsis with or without IL-7 treatment. Thymic output and the numbers of naive and effector/memory CD4+ and CD8+ lymphocytes quickly recovered after sepsis. IL-7 treatment resulted in an accelerated recovery of CD8+ lymphocytes. Next generation sequencing revealed no significant narrowing of the T cell receptor repertoire 3.5 months after sepsis. In contrast, detailed functional analyses of T helper (Th)-cell responses towards a fungal antigen revealed a significant loss of Th cells. Whereas cytokine production was not impaired at the single cell level, the absolute number of Th cells specific for the fungal antigen was reduced. Our data indicate a clinically relevant loss of pathogen-specific T cell clones after sepsis. Given the small number of naive T lymphocytes specific for a given antigen, this decrement of T cell clones remains undetected even by sensitive methods such as deep sequencing. Taken together, our data are compatible with long lasting impairments in CD4+ T-cell responses after sepsis despite rapid recovery of T lymphocyte populations. [ABSTRACT FROM AUTHOR]

Sepsis, defined as life‐threatening organ dysfunction due to a dysregulated host response to infection, is recognised by the World Health Organization as a global health priority. Each year, 5000 of the 18 000 adults with sepsis treated in Australian intensive care units die, with survivors suffering long‐term physical, cognitive and psychological dysfunction, which is poorly recognised and frequently untreated. There are currently no effective pharmacological treatments for sepsis, making early recognition, resuscitation and immediate treatment with appropriate antibiotics the key to reducing the burden of resulting disease. The majority of sepsis, around 70–80%, is community acquired making emergency departments and primary care key targets to improve recognition and early management. Case fatality rates for sepsis are decreasing in many countries with the reduction attributed to national or regional screening and quality improvement programmes focused on early identification and immediate treatment. The optimum approach to treating established sepsis has been informed by high‐quality, multicentre investigator initiated randomised trials with much of the valuable data coming from National Health and Medical Research Council‐funded trials run from Australia. While early recognition and improved management of the acute episode are important steps in reducing death and disability from sepsis, a substantial reduction in the burden of sepsis‐related disease requires action across the entire healthcare system. In this narrative review, we provide a summary of current knowledge on epidemiology of sepsis and septic shock and recommendations on the optimum approach to the management of these conditions in adults. [ABSTRACT FROM AUTHOR]

The mortality of patients with sepsis and septic shock is still unacceptably high. An effective calculated antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed infection and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account during the selection of anti-infective treatment. Many pathophysiologic alterations influence the pharmacokinetics (PK) of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of β‑lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM, but for continuous infusion, TDM is generally necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug-resistant (MDR) pathogens in the intensive care unit. For effective treatment, antibiotic stewardship teams (ABS teams) are becoming more established. Interdisciplinary cooperation of the ABS team with infectious disease (ID) specialists, microbiologists, and clinical pharmacists leads not only to rational administration of antibiotics, but also has a positive influence on treatment outcome. The gold standards for pathogen identification are still culture-based detection and microbiologic resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction(PCR)-based procedures for pathogen identification and resistance determination are currently only an adjunct to routine sepsis diagnostics, due to the limited number of studies, high costs, and limited availability. In complicated septic courses with multiple anti-infective therapies or recurrent sepsis, PCR-based procedures can be used in addition to treatment monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically (still) absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation). (Contribution available free of charge by "Free Access" [ https://link.springer.com/article/10.1007/s00101-017-0396-z ].). [ABSTRACT FROM AUTHOR]

Abstract This paper outlines a simple label-free sensor system for the sensitive, real time measurement of an important protein biomarker of sepsis, using a novel microelectrode integrated onto a needle shaped substrate. Sepsis is a life threatening condition with a high mortality rate, which is characterised by dysregulation of the immune response following infection, leading to organ failure and cardiovascular collapse if untreated. Currently, sepsis testing is typically carried out by taking blood samples which are sent to a central laboratory for processing. Analysis times can be between 12 and 72 h making it notoriously difficult to diagnose and treat patients in a timely manner. The pathobiology of sepsis is becoming increasingly well understood and clinically relevant biomarkers are emerging, which could be used in conjunction with a biosensor to support real time diagnosis of sepsis. In this context, microelectrodes have the analytical advantages of reduced iR drop, enhanced signal to noise ratio, simplified quantification and the ability to measure in hydrodynamic situations, such as the bloodstream. In this study, arrays of eight (r = 25 µm) microelectrodes were fabricated onto needle shaped silicon substrates and electrochemically characterised in order to confirm successful sensor production and to verify whether the observed behaviour agreed with established theory. After this, the electrodes were functionalised with an antibody for interleukin-6 (IL-6) which is a protein involved in the immune response to infection and whose levels in the blood increase during progression of sepsis. The results show that IL-6 is detectable at physiologically relevant levels (pg/mL) with incubation times as short as 2.5 min. Electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) measurements were taken and DPV was concluded to be the more suitable form of measurement. In contrast to the accepted view for macro electrodes that the impedance increases upon antigen bind, we report herein a decrease in the micro electrode impedance upon binding. The small size of the fabricated devices and their needle shape make them ideal for either point of care testing or insertion into blood vessels for continuous sepsis monitoring. Highlights • An array of 8 × 50 µm gold electrodes were fabricated onto a needle shaped substrate. • The device was electrochemically characterised to confirm successful fabrication and demonstrate microelectrode behaviour. • Interleukin 6 (IL-6) antibody was immobilised onto the electrode surface. • EIS & DPV measurements were demonstrated as effective methods for detection of antibody- antigen binding. • A dose response curve was established showing IL-6 could be measured at normal and elevated levels using DPV. [ABSTRACT FROM AUTHOR]